An opioid is a chemical substance that has morphine-like action in the body. The main therapeutic use of opioids is for pain relief. These agents are thought to work primarily by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract.
Drug powders containing micron-size drug particles are used in several pharmaceutical dosage forms. Many drugs, especially newly developed substances, are poorly water soluble, which limits their oral bioavailability. This is not true for the salt forms of opioids which are generally soluble. The dissolution rate of insoluble drugs can be enhanced by using micronized drugs. Small drug particles are also required in certain administration forms, which require the drug in micron-size due to the geometric reasons in the organ to be targeted (e.g., drugs for pulmonary use). Again, this is not true for opioids, which are generally administered orally or by injection. The common technique for the preparation of micron-size drugs is the mechanical comminution (e.g., by crushing, grinding, and milling) of previously formed larger particles.
In spite of the use of these techniques, the micronization process can be problematic for the production of small particles because drug substance properties including, for example, surface properties are altered in a mainly uncontrolled manner. For example, the surface of the crystal structure of a micronized particle may be affected in such a manner to make it relatively unstable. In particular, micronized particles may lose their native particle surface crystalline structure by conversion, in varying degrees, to amorphous solid during micronization, upon storage, rendering the particles less stable in their solid state. For example, even the presence of small amounts of an amorphous material in a micronized particle preparation, such as a powder of micronized salbutamol sulfate, has been reported by Brodka-Pfeiffer et al., 2003, Drug Development and Industrial Pharmacy, 29(10):1077-1084, to have deleterious effects on the physical stability of the powder. Amorphous material tends to recrystallize, and lead to particle growth outside a desired particle distribution range in a product including rendering particles unable to reach target tissues or preventing their usefulness in the preparation of pharmaceutical formulations or dosage forms.